tbuckley/cabot-search huggingface dataset:
Concordance between liquid and tissue biopsy in participants with newly diagnosed recurrent breast cancer.
Authors: Ana Elisa Lohmann, Marguerite Ennis, Pamela Jean Goodwin, Zachary William Neil Veitch, Christine Brezden, Katarzyna Joanna Jerzak, Kathie Baer, Samuel Martel, Julie Lemieux, Jose Luiz Miranda Guimaraes, David W. Cescon, Michael P. Thirlwell, Megan Slade, Giuseppe Di Caro, Rick Wenstrup, Josee-Lyne Ethier, Sara V. Soldera
Journal: Journal of Clinical Oncology (2023)

1028 Background: Tissue biopsy is recommended to confirm breast cancer (BC) recurrence. Liquid biopsy [including circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA)] is a non-invasive approach for detecting cancer that may provide information to identify treatment choices and replace invasive biopsies. This ongoing study aims to assess the concordance between tissue and liquid biopsy testing in subjects presenting with suspicion of distant recurrence from BC. Methods: Patients with suspected metastatic BC were enrolled; tumour characteristics and treatment were recorded. Blood samples were collected within 30 days before tissue biopsy, or within 7-28 days after tissue biopsy and before any systemic or radiation treatment. Samples were shipped to EPIC Sciences and processed within 96 hours; after plasma isolation, nucleated cells were plated; slides and plasma were banked. CTCs were identified using Epic Sciences digital imaging and machine learning algorithms. Single-cell isolation for genomic ctDNA analysis was performed. Cell free DNA was analyzed using a validated NGS panel to detect ctDNA alterations. The presence of metastases was classified as suspicious, highly suspicious, definitely metastatic BC or other by the treating oncologist based on the patient's clinical presentation and biopsy pathology results. Epic Sciences classified samples into similar categories based on CTC and ctDNA assay results. These classifications were performed independently. Sensitivity of the Epic Sciences methodology to detect metastatic BC (as determined by the treating oncologist), and its false positive rate were calculated. Results: 100 patients were enrolled from June 2020 to October 2022; shipping delays precluded EPIC assays in six patients; 94 patients were analyzed. Of 83 cases deemed suspicious, highly suspicious, or definitely metastatic BC by the treating oncologist, 61 were also deemed so by Epic Sciences (sensitivity of 73.5%, 95% confidence interval, CI 63.1% - 81.9%). Of 66 cases assigned as suspicious, highly suspicious, or definitely metastatic BC by the Epic Sciences, 4 had new primary cancers (3 lung cancer, 1 hepatocarcinoma), for a false positive rate of 6.1% (95% CI 1.9% - 15.0%). One additional case was classified as un-specified adenocarcinoma (possibly breast) by the treating oncologist; resolution awaits further follow-up. Conclusions: Preliminary results show that 73.5% of distant BC recurrences were correctly identified by liquid biopsy. A small number of false positive results occurred in patients with other new primary cancers. Additional analyses with CTC characterization are ongoing. [Table: see text]
An AI tool for chest X-ray interpretation and lung cancer pre-screening in developing countries.
Authors: Iván Romarico González Espinoza, Jorge Alatorre-Alexander, Diego A. Juárez-Salazar, Abraham Castro-Ponce, Gabriela Juárez-Salazar, Diego A. Martínez-Hernández, Edgar E. Cardona-Ferrer, Laura E. González-Lozada, Enrique Miguel Cruz, Sergio Sánchez-Sosa, Eric Acosta Ponce de León, Mariana Chiquillo-Domínguez
Journal: Journal of Clinical Oncology (2023)

1548 Background: The current lung cancer screening strategy has not had a major impact on public health, facing many challenges during its implementation in developing countries. Although chest radiography (CXR) is not the study of choice for screening; it is one of the most accessible studies used at all levels of care, so implementing an AI tool capable of CXR interpretation as well as lung cancer risk assessment on a large scale could improve the selection of patients for lung cancer screening. The aim of our study was to develop and evaluate this tool. Methods: The dataset used for this tool development was obtained from the NIH "ChestX-ray14” public database. The set was divided into 3 subgroups for training, testing, and validation in a ratio of 80/10/10% respectively. We performed a structuration of metadata and an exploratory analysis as well as preprocessing of the images to standardize their size and resolution before the training. A model based on the adaptation of the momentum for learning was used as an optimizer of the CNN algorithm used. Additionally, a questionnaire based on the PLCO clinical criteria was included for the identification of patients at high risk of developing lung cancer. Results: Standard performance metrics were evaluated as shown. Conclusions: Our model is comparable to certified radiologists in accuracy at identifying patterns of a CXR. The use of clinical patient information improves the pre-selection of patients with a high risk of developing lung cancer. In developing countries, the implementation of this tool on a large scale will allow more patients to be screened and early diagnosed.[Table: see text]
Prognostic significance of estrogen receptor status in de novo metastatic breast cancer.
Authors: Ren Chongxi, Sun Jianna, Kong Lingjun, Luo Ruizhen, Mu Kun, Jiang Xiuzhen
Journal: Journal of Clinical Oncology (2023)

e13049 Background: The clinical behaviors of de novo metastatic breast cancer (dnMBC) differ according to hormone receptor (HR) status, but an association between estrogen receptor (ER) expression and clinical outcomes has not been established. Our study aimed to investigate the influence of different ER status on survival outcomes for patients with dnMBC. This study was the Medical Science Research Project of Hebei Province and approved by the Ethics Committee of the Ethics Committee of Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University (NO. 2017-AF29-058). Methods: Using hospital-based database, we identified patients with dnMBC diagnosed between 2010 and 2017, retrospectively collecting demographic data, tumor characteristics, treatment types and survival data. According to ER status, the patients were divided into ER-negative and ER-positive groups, and the propensity score matching (PSM) was used to balance the mixed bias. Overall survival (OS) was estimated by Kaplan-Meier method and log rank test. Univariable and multivariable analyses were performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Results: A total of 322 patients were included. The median age was 53 (21-82) years, and the median follow-up was 8.5 years. The median OS for the PSM cohort was 29 months (95% confidence interval [CI], 26-35 months), and 5-year OS was 18.9%. OS differed significantly between the two groups (p = 0.0012), with a median OS of 36 months (95% CI, 32-41 months) in ER-positive group and 24 months (95% CI, 19-27 months) in ER-negative group. Multivariate analysis showed that clinical T-stage and initial metastatic sites were independent prognostic factors for survival in patients focused on ER status, with Ki-67 index, endocrine therapy and radiotherapy added to the ER-positive group, while initial and advanced chemotherapy added to the ER-negative group. Conclusions: For patients with dnMBC, there were substantial differences in OS according to ER status. ER-negative subtype is clinically different from ER-positive subtype, showing unfavorable tumor characteristics and poorer OS. We identified several prognostic factors that could guide therapy selection in this patient population. Clinical trial information: 20210957 .
Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma: The EORTC 1608 STEAM trial.
Authors: Emilie Le Rhun, Thierry Gorlia, Julia Furtner, Joerg Felsberg, Joost Jongen, Claude-Alain Maurage, Francois Ducray, Patrick Roth, Peter Hau, Olivier L. Chinot, Matthias Preusser, Stephanie Cartalat, Martin J. Van Den Bent, Maike Collienne, Guido Reifenberger, Michael Weller
Journal: Journal of Clinical Oncology (2023)

2054 Background: Zotiraciclib (TG02) is an oral multi-cyclin dependent kinase (CDK) inhibitor, including CDK-9, that inhibits tumor growth down-stream via depletion of survival proteins such as MCL-1 and MYC. MCL-1 and MYC are frequently overexpressed in glioblastoma. Methods: The EORTC 1608 (NCT03224104) (STEAM) phase 1b trial had a three parallel group (A,B,C) open-label, non-randomized, multicenter design. Groups A and B explored the maximum tolerated dose (MTD) of zotiraciclib in elderly patients (more than 65 years) with IDH1 R132H -non-mutant newly diagnosed glioblastoma or anaplastic astrocytoma, in combination with hypofractionated radiotherapy alone (group A) or temozolomide alone (group B), based on O 6 -methylguanine DNA methyltransferase promoter methylation status determined centrally. Group C explored single agent activity of zotiraciclib in IDH1 R132H -non-mutant glioblastoma or anaplastic astrocytoma at first relapse after temozolomide chemoradiotherapy with a primary endpoint of progression-free survival at 6 months. Secondary objectives included efficacy, quality of life, and safety. Results: The MTD was 150 mg in combination with radiotherapy alone (group A, n=12) or temozolomide alone (group B, n=9) in elderly patients. Two dose-limiting toxicities were observed at 150 mg, one in group A (grade 3 seizure) and one in group B (multiple grade 1 events). Main toxicities included neutropenia, gastro-intestinal disorders, and hepatotoxicity. Progression-free survival at 6 months in group C (n=50) was 6.7%. Conclusions: Zotiraciclib exhibits overlapping toxicity with alkylating agents and low clinical activity as a single agent. Larger randomized trials may be required to explore activity in combination with radiotherapy or temozolomide. Clinical trial information: NCT03224104 .
Real-world experience with tumor treating fields (TTFields) in newly diagnosed glioblastoma: A survival meta-analysis with systematic review.
Authors: Matthew T. Ballo, Patrick Conlon, Gitit Lavy-Shahaf, Noa Urman, Adrian Kinzel, Josef Vymazal, Aaron Rulseh
Journal: Journal of Clinical Oncology (2023)

2059 Background: Tumor Treating Fields (TTFields) are electric fields that exert forces on cancer cells, disrupting processes critical for cancer cell viability and tumor progression. TTFields therapy became an FDA-approved treatment option for patients with newly diagnosed glioblastoma (GBM) in 2015 on the basis of the randomized controlled EF-14 study (NCT00916409). Subsequent approvals worldwide and increased adoption of TTFields has led to the question of whether or not a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role. Methods: A literature search was conducted using PubMed, Embase, and the Cochrane Library to identify clinical studies evaluating overall survival in adult patients with GBM treated with TTFields therapy. Comparative studies and single-cohort studies reporting on survival outcomes were included in the analysis. Inter-study heterogeneity was assessed using the Cochran Q test and quantified using the Higgins I 2 statistic. Survival curves were pooled using a distribution-free random-effects method. Results: Our review identified 8 studies evaluating the clinical efficacy of TTFields therapy in newly diagnosed GBM, with patients spanning diverse geographic regions. Of these 8, 6 studies (reporting on a total of 1378 patients) compared the addition of TTFields therapy to standard of care (SOC) vs SOC alone, and were included in a pooled analysis for overall survival. Meta-analysis of comparative studies indicated a significant improvement in overall survival for patients treated with TTFields therapy vs those not receiving treatment (hazard ratio [HR]: 0.62; 95% CI, 0.52–0.73; P &lt; 0.001). Inter-study heterogeneity was examined, and a sensitivity analysis indicated the pooled effect was robust and not dependent on any individual study. Among post-approval studies, the pooled median overall survival was 22.2 months (95% CI, 17.3–42.6) for TTFields-treated patients and 17.3 months (95% CI, 13.6–22.0) for the non-TTFields group. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, among studies reporting data on TTFields device usage, an average device usage rate of 75% or higher was found to consistently associate with prolonged survival when compared to an average usage rate below 75% (pooled HR: 0.63; 95% CI, 0.48–0.83; P = 0.001). Conclusions: Meta-analysis of comparative studies suggests a significant survival benefit with TTFields therapy added to standard radiochemotherapy for patients with newly diagnosed GBM, and that a 75% usage rate may be meaningful in the real-world setting.
Symptom burden of patients with breast cancer on adjuvant hormone therapy: A preliminary report.
Authors: Sameh Gomaa, Ana Maria Lopez, Rita Smith, Rachel Slamon, Kuang-Yi Wen
Journal: Journal of Clinical Oncology (2023)

e12536 Background: Breast cancer (BCa) is the most common cancer in women. Adjuvant hormone therapy (AHT) showed consistent improvements in recurrence and survival rates. AHT use is associated with multiple side effects that cause a lack of adherence. This report aims to describe the symptom burden of BCA patients at treatment initiation from our ongoing RCT, which is directed at improving adherence through the innovative use of smart pill bottles. Methods: Descriptive statistics included socio-demographic information and medication use. Symptom burden and distress are assessed using the breast cancer prevention trial (BCPT) symptom scales. Self-efficacy is assessed using a modified version of Lorig’s Chronic Disease Self-Efficacy Scale for managing symptoms. Results are summarized as means (M), standard deviation (SD), ranges (R), and percentages. The relationship between patients’ symptoms and self-efficacy was analyzed using a multivariable linear regression model controlling for age and race. Results: Of the 119 patients included, the majority were White 80.7 %, with ages ranging from 31-81 with a mean age of 59.74 (SD=11.057). The majority had a college education or higher (61.3 %), married (66.4%), full-time workers (42.9 %) and had incomes of 75,000 USD or higher (59.0 %). The patients were on either Tamoxifen (17.7%), Anastrozole (55.4%), Letrozole (12.3%) or Exemestane (4.6 %). The (BCPT) subscales were; vasomotor symptoms (R=0-12.5, M= 5.8, SD= 3.14), Gastrointestinal symptoms (R=0-7.5, M= 2.97, SD= 1.14), bladder control (R=0-10, M= 3.09, SD= 1.87), Dyspareunia subscale (R=0-10, M= 3.53, SD= 2.27), Musculoskeletal pain (R=0-15, M= 7.5, SD= 3.53), Weight concerns (R=0-10, M= 4.22, SD= 2.16), Cognitive symptoms (R=0-15, M= 6.02, SD= 2.81). For the LORIG scales (R=1- 8.83, M= 6.04, SD=1.61). Patient symptoms were inversely correlated with higher LORIG scores for vasomotor symptoms (β = -.18, t(3) = -2.00, p= .048), Gastrointestinal symptoms (β = -.27, t(3) = -2.92, p= 0.004), Musculoskeletal pain (β = -.378, t(3) = -4.31, p= .000), Weight concerns (β = -.286, t(3) = -3.26, p= .0002), Cognitive symptoms (β = -.34, t(3) = -3.841, p= .000). Conclusions: Our results explore symptom burden and distress for breast cancer patients on AET. Based on the BCPT instrument subscales, musculoskeletal symptoms tend to be the most intrusive, with the highest mean score. Symptom burden was inversely related to higher self-efficacy represented by LORIG scores. This needs to be validated with further analysis in comparison to a control group across time points in the study to determine what would be a minimally important difference or change in score. This will help understand the interrelationships between physical symptoms and adherence to AHT. Clinical trial information: NCT04086875 .
Taxane combined with lobaplatin or anthracycline for neoadjuvant treatment of triple-negative breast cancer: A single-center, randomized, controlled, phase-II clinical study.
Authors: Cheng Wang, Rui Wang, Guozhi Zhang, Andi Wan, Siyi Xiong, Long Yuan, Hao Tian, Dandan Ma, Jun Jiang, Yi Zhang, Xiaowei Qi
Journal: Journal of Clinical Oncology (2023)

593 Background: Previously, we showed that addition of lobaplatin (L) to taxane combined with anthracycline could improve the pathologic complete response (pCR) rate and lengthen survival significantly if employed as neoadjuvant therapy in patients with triple-negative breast cancer (TNBC). We evaluated the efficacy and safety of neoadjuvant chemotherapy of taxane (T) combined with lobaplatin (L) or anthracycline (E) for patients with TNBC. Methods: Ninety-five patients with TNBC (stage I–III) who had not undergone any type of treatment were divided randomly into two groups: TL (docetaxel at 75 mg/m 2 and lobaplatin at 30 mg/m 2 , D1, one cycle = 21 days, a total of six cycles) or TE (docetaxel at 75 mg/m 2 and epirubicin at 80 mg/m 2 , D1, one cycle = 21 days, a total of 6 weeks or epirubicin at 80 mg/m 2 and cyclophosphamide at 600 mg/m 2 , sequential docetaxel at 75 mg/m 2 , D1, one cycle = 21 days, a total of eight cycles). Efficacy was evaluated every two cycles. The final surgical procedure was completed after fulfillment of neoadjuvant chemotherapy. The primary endpoint was the total pathologic complete response (tpCR) rate. The secondary endpoints were the objective response rate (ORR), safety, event-free survival (EFS), and overall survival (OS). The exploratory endpoint was biomarker analysis. Results: From June 2019 to November 2022, 97 patients were screened. Finally, 95 patients were enrolled. The median age of the study cohort was 49 years. Nine patients (9.5%) had stage-I disease, 61 patients (64.2%) had stage II, and 25 patients (26.3%) had stage III. Sixty-five patients (68.4%) had Ki67 ≥40% and 30 patients (31.6%) had Ki67 &lt; 40%. Seventy patients (73.7%) were cytokeratin (CK)5/6+ and 25 patients (26.3%) were CK5/6−. Of 95 patients, 47 were in the TL group and 48 in the TE group. The tpCR rate in the TL group was 46.8% (22/47), which was significantly higher than that in the TE group (22.9% (11/48); odds ratio (OR) = 2.960, 95% confidence interval (CI) = 1.223–7.164, P = 0.016). The ORR in the TL group was 95.7% (45/47), which was significantly higher than that in the TE group (75.0% (36/48); OR = 27.500, 95% CI = 1.576–35.683, P = 0.011). The prevalence of grade III/IV neutropenia in the TE group was 41.0% (9/22), which was significantly higher than that in the TL group (7.7% (2/26); OR = 8.308, 95% CI = 1.557–44.320, P = 0.013). There was no significant difference in the prevalence of other adverse reactions between the two groups. Conclusions: In the neoadjuvant treatment of TNBC, the TL regimen had a higher tpCR rate and ORR than those of the TE regimen, and was safer. Clinical trial information: ChiCTR1900023776 .
INSIGHT-HER2BC: Real-world evidence of TCHP regimen to describe the best patient profile and open up questions—The interim results.
Authors: Lyudmila Zhukova, Irina Sorokina, Anastasia Danilova, Alexander Yurchenkov, Ilya Pokataev, Irina Alekseenko, Daniil Stroyakovsky
Journal: Journal of Clinical Oncology (2023)

e12607 Background: Neoadjuvant therapy (NAT) of TCHP regimen is approved for standard therapy for early and locally advanced HER2-positive breast cancer (eHER2+ BC) based on encourage TRYPHAENA and KRISTINE trials results. There are limited data regarding patients (pts) treatment outcomes after NAT TCHP in the routine clinical practice. Here we presented the 1 st results of ambispective observational program to assess the efficacy and safety of cancer therapy in patients with solid tumors. Early HER2+ breast cancer group: INSIGHT-HER2BC. Methods: We ambispectively reviewed medical records of pts with eHER2+ BC who underwent NAT 6xTCHP (6 docetaxel/carboplatin + trastuzumab/pertuzumab) at three Moscow oncology centers since Jan’2017. This ongoing trial has launched in Feb’22. Here is presented descriptive analyses of pCR (ypT0/is, ypN0) rate for pts who completed NAT and 1-3 yrs. disease-free survival (DFS). Results: At the data cut-off (Jan’2023) 934 pts with HER2+ eBC underwent ≥ 1 cycle of NAТ. The median age is 54.3 y.o. (range: 22-78) where 36% pts were older 60 y.o.; 14% pts - younger than 40 y.o. 75% (571) pts had surgery results. pCR rate is related to KRISTINE trial: 58% (330) pts in the ITT (intention-to-treat) population vs 56% pts, respectively. pCR rate for pts with locally advanced BC is 55% vs 59% for operable BC (114/208 and 215/363 pts, respectively). There is difference in pCR rate achievement according to hormone status (HR+ vs HR-) and HER2 status (3+ vs 2+/ISH +). 1-yr. DFS for pCR group is 97% vs 94% for non-pCR; 2-yr. DFS is 83% vs 83%, respectively, and 3-yr. DFS 64% for pCR group vs 58% for non-pCR. In HR-HER2+ BC the biggest drop between pCR and non-pCR is registered at the 3-yr. DFS: 56% vs 22% while in HR+HER2+ there is almost equal decrease was observed every yr.: 97% vs 93% - 1 st yr.; 90% vs 85% - 2 nd yr.; 72% vs 68% - 3 d yr. Conclusions: NAT TCHP is the effective regimen for HER2+ eBC in the real-world population. The efficiency is observed regardless of disease stage and age. However, there is clear unmet need to find new therapeutic options for HER2 (2+/ISH+) BC. Preliminary results of DFS is markedly lower than in TRYPHAENA and KRISTINE trials but in conjunction with another real-world evidence data. DFS in HR+HER2+ and HR-HER2+ pts likely reflects distinct tumor biology. The mature data for long-term outcomes are awaited. [Table: see text]